Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 60, Issue 7, Pages 813-823Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2007.11.004
Keywords
adjuvant; dendritic cells; immune response modifiers; innate immunity; pathogen-associated molecular patterns; pattern recognition receptors; Toll-like receptors; virus
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Funding
- Cancer Research UK Funding Source: Medline
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The Toll-like receptors (TLR), mediating innate immune activation upon recognition of viral nucleic acids, represent promising targets for the development of adjuvants. Therefore, there is great interest in unraveling the underlying mechanisms of ligand recognition. Studies aiming to identify which sequences, nucleic acid modifications and molecular moieties of viral nucleic acids trigger or inhibit TLR activation have allowed insights into this subject, yet there are still many aspects of innate recognition of viral nucleic acids which are only partially understood. This review discusses our current understanding of TLR-mediated recognition of viral single-stranded RNA (ssRNA) by TLR7 and TLR8. Oligoribonucleotides (ORN) and small immune response modifiers such as imidazoquinolines with agonist function have served as tools to study ligand recognition. In addition, there is increasing evidence that TLR-mediated recognition of mammalian ssRNA triggers innate immune activation and plays a role in autoimmunity. Thus the development of suitable TLR7 and TLR8 antagonists could pave the way for therapeutic intervention of particular autoimmune diseases. (c) 2008 Elsevier B.V. All rights reserved.
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